Redox-Based Strategy for Selectively Inducing Energy Crisis Inside Cancer Cells: An Example of Modifying Dietary Curcumin to Target Mitochondria
| Autor: | Ya-Long Zheng, Zhi-Shan Tu, Hong-Mei Cui, Shuai Yan, De-Chen Duan, Wei Tang, Fang Dai, Bo Zhou |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Agricultural and Food Chemistry. 70:2898-2910 |
| ISSN: | 1520-5118 0021-8561 |
| Popis: | Reprograming of energy metabolism is a major hallmark of cancer, but its effective intervention is still a challenging task due to metabolic heterogeneity and plasticity of cancer cells. Herein, we report a general redox-based strategy for meeting the challenge. The strategy was exemplified by a dietary curcumin analogue (MitoCur-1) that was designed to target mitochondria (MitoCur-1). By virtue of its electrophilic and mitochondrial-targeting properties, MitoCur-1 generated reactive oxygen species (ROS) more effectively and selectively in HepG2 cells than in L02 cells via the inhibition of mitochondrial antioxidative thioredoxin reductase 2 (TrxR2). The ROS generation preferentially mediated the energy crisis of HepG2 cells in a dual-inhibition fashion against both mitochondrial and glycolytic metabolisms, which could hit the metabolic plasticity of HepG2 cells. The ROS-dependent energy crisis also allowed its preferential killing of HepG2 cells (IC |
| Databáze: | OpenAIRE |
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